Salmonella is a common and important pathogen that kills millions of people each year, primarily children in developing countries. It was the first organism to be used as a bioterrorist weapon in the US and is listed as category B in the NIH list of BT agents (S. enterica as we describe here). The primary goal of my research is to use Salmonella as a model to understand how intracellular pathogens manipulate host cells to cause disease. Using our expertise with the Salmonella/macrophage model, coupled with genetics, molecular biology and transcriptional profiling, we will further our understanding of how intracellular pathogens regulate virulence gene expression. Our hypothesis is that multiple regulators respond to different cues within cells and that the signal becomes integrated, perhaps by one or a few master regulators, to express specific subsets of virulence factors required for survival and growth within different cells and tissues of the host. Salmonella is a model for studying intracellular pathogenesis without equal because of its established genetics and simple and inexpensive animal model - the mouse. Understanding how Salmonella survives and replicates within the host and how it expresses virulence genes at the appropriate time and place during infection will identify new therapeutic targets and provide a paradigm for understanding other pathogens.

Public Health Relevance

Salmonella is a common and important pathogen that kills millions of people each year, primarily children in developing countries. We wish to understand how Salmonella survives within and manipulates host cells for its own benefit. The goal of this research is to discover how Salmonella expresses virulence genes at the appropriate time and place during the infection in order to identify new therapeutic targets and to provide a paradigm for understanding other intracellular pathogen.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI022933-24
Application #
7994183
Study Section
Special Emphasis Panel (ZRG1-BACP-H (02))
Program Officer
Alexander, William A
Project Start
1987-04-01
Project End
2013-11-30
Budget Start
2010-12-01
Budget End
2011-11-30
Support Year
24
Fiscal Year
2011
Total Cost
$423,256
Indirect Cost
Name
Oregon Health and Science University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239
Li, Jie; Overall, Christopher C; Nakayasu, Ernesto S et al. (2015) Analysis of the Salmonella regulatory network suggests involvement of SsrB and H-NS in ?(E)-regulated SPI-2 gene expression. Front Microbiol 6:27
Deatherage Kaiser, Brooke L; Li, Jie; Sanford, James A et al. (2013) A Multi-Omic View of Host-Pathogen-Commensal Interplay in Salmonella-Mediated Intestinal Infection. PLoS One 8:e67155
Kidwai, Afshan S; Mushamiri, Ivy; Niemann, George S et al. (2013) Diverse secreted effectors are required for Salmonella persistence in a mouse infection model. PLoS One 8:e70753
Hovis, Kelley M; Mojica, Sergio; McDermott, Jason E et al. (2013) Genus-optimized strategy for the identification of chlamydial type III secretion substrates. Pathog Dis 69:213-22
Nakayasu, Ernesto S; Brown, Roslyn N; Ansong, Charles et al. (2013) Multi-omic data integration links deleted in breast cancer 1 (DBC1) degradation to chromatin remodeling in inflammatory response. Mol Cell Proteomics 12:2136-47
Ansong, Charles; Deatherage, Brooke L; Hyduke, Daniel et al. (2013) Studying Salmonellae and Yersiniae host-pathogen interactions using integrated 'omics and modeling. Curr Top Microbiol Immunol 363:21-41
Niemann, George S; Brown, Roslyn N; Mushamiri, Ivy T et al. (2013) RNA type III secretion signals that require Hfq. J Bacteriol 195:2119-25
Brown, Roslyn N; Sanford, James A; Park, Jea H et al. (2012) A Comprehensive Subcellular Proteomic Survey of Salmonella Grown under Phagosome-Mimicking versus Standard Laboratory Conditions. Int J Proteomics 2012:123076
Archuleta, Michelle N; McDermott, Jason E; Edwards, Jeremy S et al. (2012) An adaptive coarse graining method for signal transduction in three dimensions. Fundam Inform 118:
McDermott, Jason E; Corrigan, Abigail; Peterson, Elena et al. (2011) Computational prediction of type III and IV secreted effectors in gram-negative bacteria. Infect Immun 79:23-32

Showing the most recent 10 out of 57 publications